tbuckley/cabot-search huggingface dataset:
P11.24.A The anisotropic component of the decomposed diffusion tensor predicts overall survival in patients with glioblastoma
Authors: N L Simon, R Sinha, S Sravanam, R Mayrand, C Li, Y Wan, Y Wei, S Price
Journal: Neuro-Oncology (2022)

Abstract Background The diffusion tensor can be decomposed into isotropic (DTI-p) and anisotropic (DTI-q) components (Peña et al., 2006). Regions of DTI-q abnormality have a high tumour burden and increased surgical resection of abnormal DTI-q positively correlates with overall survival (OS) (Yan et al., 2017). We aimed to establish if median voxel DTI-q (MVQ) or a distribution measure of DTI-q (DMQ) could act as a neuro-imaging biomarker, to predict OS in patients with glioblastoma. Material and Methods Diffusion tensor decomposition was used to create DTI-p and DTI-q maps, using FSL software (FMRIB Software Library, Oxford). MVQ and DMQ (the 95th centile minus the 5th centile of the DTI-q distribution, divided by the MVQ) were calculated from the preoperative whole brain (WB), contrast-enhancing (CE), and non-contrast-enhancing (NCE) hemisphere DTI-q maps, using fslstats, for 33 patients with glioblastoma. Using R Studio, multiple linear regression (MLR) models were computed to establish if MVQ or DMQ of the WB, CE and NCE hemispheres or age, significantly predicts OS. The Breusch-Pagan Test, on package “lmtest” in R, was calculated for all MLR models, to determine if heteroscedasticity was present and, if so, bootstrapped multiple regression (BMR) models were computed using package “boot” in R. Results Evidence for heteroscedasticity was present in MLRs that modelled the relationship between DMQ of WB, age, and OS (BP = 6.032, p = 0.014) and DMQ of CE hemisphere, age, and OS (BP = 7.163, p = 0.028). In the BMR of WB DMQ, age, and OS, the 95% bias-corrected accelerated confidence intervals (BCa-CI) for the WB DMQ regression coefficient was 133.5 - 1851.4 and included the WB DMQ estimated coefficient of 803.9. The BMR of CE hemisphere DMQ, age, and OS, computed a 95% BCa-CI for the CE hemisphere DMQ coefficient of 101.8 - 1579.6, containing the CE hemisphere DMQ coefficient estimate of 612.414. For both BMRs, the 95% BCa-CI for age coefficients crossed a value of 0. From computed MLR models, WB MVQ (t = -2.569, p = 0.015), CE hemisphere MVQ (t = -2.143, p = 0.040), NCE hemisphere MVQ (t = -2.567, p = 0.015) and NCE hemisphere DMQ (t = 2.39, p = 0.024) were significant predictors of OS. Age did not significantly predict OS in any models and was not significantly related to WB, CE and NCE hemisphere MVQ or DMQ. Conclusion WB, CE and NCE hemisphere MVQ and DMQ predict OS in our tested subgroup of patients with glioblastoma. Age is not a significant predictor of OS and does not significantly correlate with MVQ or DMQ. The median value and distribution spread of DTI-q may act as a prognostic biomarker in glioblastoma, facilitating patient stratification.
P11.62.A The link between gliomas infiltrationandwhite matter architecture investigated with electron microscopy and diffusion tensor imaging
Authors: F Latini, M Fahlström, A Beháňová, I Sintorn, M Hodik, K Staxäng, M Ryttlefors
Journal: Neuro-Oncology (2022)

Abstract Background Diffuse low-grade gliomas (DLGG) display different preferential locations in eloquent and secondary associative brain areas. The reason for this tendency is still unknown. We hypothesized that the intrinsic architecture and water diffusion properties of the white matter bundles in these regions may facilitate gliomas infiltration. Material and Methods Magnetic resonance imaging of sixty-seven diffuse low-grade gliomas patients were normalized to/and segmented in MNI space to create three probabilistic infiltration weighted gradient maps according to the molecular status of each tumor group (IDH mutated, IDH wild-type and IDH mutated/1p19q co-deleted). Diffusion tensor imaging (DTI)- based parameters were derived for five major white matter bundles, displaying regional differences in the grade of infiltration, averaged over 20 healthy individuals acquired from the Human connectome project (HCP) database. Transmission electron microscopy (TEM) was used to analyze fiber density, fiber diameter and g-ratio in 100 human white matter regions, sampled from cadaver specimens, reflecting areas with different gliomas infiltration in each white matter bundle. Histological results and DTI-based parameters were compared in anatomical regions of high- and low grade of infiltration (HIF and LIF) respectively. Results We detected differences in the white matter infiltration of five major white matter bundles in three groups. IDHm infiltrated left fronto-temporal subcortical areas. IDHwt were detected in the posterior-temporal and temporo-parietal regions bilaterally. IDHm/1p19q infiltrated anterior subcortical regions of the frontal lobes bilaterally. Regional differences within the same white matter bundles were detected by both TEM- and DTI analysis linked to different topographical variables. Our multimodal analysis showed that HIF regions, common to all the groups, displayed a smaller fiber diameter, lower FA and higher RD compared with LIF regions. Conclusion Our results suggest that the both morphological features and diffusion parameters of the white matter may be different in regions linked to the preferential location of DLGG.
P18.08.B Fully automatic meningioma segmentation using T1-weighted contrast-enhanced MR images only
Authors: S M Boelders, W De Baene, G J M Rutten, K Gehring, L L Ong
Journal: Neuro-Oncology (2022)

Abstract Background Manual segmentation of brain tumors requires expertise, is time-consuming, and is subject to inter-rater variability. Fully automatic brain tumor segmentation is possible for glioma and meningioma when volumetric T1, T1 contrast-enhanced (T1c), T2, and Fluid-attenuated inversion recovery (FLAIR) MRIs are available. In clinical care of meningiomas, however, often only volumetric T1c scans are available. In this work, we trained a deep learning network to segment meningiomas using only T1c scans for use in clinical research. Material and Methods NnU-Net, a deep learning model that is optimized for medical image segmentation, was trained to segment meningiomas from T1c images. This was performed on a large clinically collected meningioma dataset (n=374) of T1c scans with semi-automatically generated enhancing tumor masks and additional data from the BraTS2020 glioma dataset. Model performance was compared against inter-rater reliability, between different models, between anatomical tumor locations, and against models using multiple MRI modalities. Results The best performing model obtained a Dice score of 0.90. This performance was 0.03 points lower when compared to inter-rater reliability (Dice=0.93) and almost equal to models using multiple MRI modalities. Model performance split over anatomical tumor locations was between 0.90 and 0.97 (Dice). Conclusion Fully automatic meningioma segmentation using only T1c images is possible with an accuracy that is similar to inter-rater reliability and models using multiple imaging modalities.
OS11.5.A Utility of lumbar puncture (LP) and cerebrospinal fluid (CSF) profile in the diagnosis of neoplastic meningitis (NM): a retrospective cohort study and meta-analyses
Authors: K J Tuohy, K Major, D Aregawi, M Glantz
Journal: Neuro-Oncology (2022)

Abstract Background CSF cytology remains the gold standard for diagnosing NM, but the sensitivity of this test is low (approximately 50% with one LP). Little is known about the predictive value of routine CSF and clinical findings for a positive cytology. We addressed these questions by analyzing 337 consecutive patients at our institution, and by conducting exhaustive evidence-based literature reviews and meta-analyses of relevant research. Material and Methods 337 consecutive patients at a single institution were evaluated. Of these, 210 met criteria for NM (a positive CSF cytology on at least one of four pre-treatment samples) or no NM (four consecutive negative CSF cytologies). CSF white blood cell count, glucose, protein, and lactate were collected, as well as the presence of neurological symptoms. Optimal threshold values were identified using ROC curves. Sensitivity (Sn), specificity (Sp), and likelihood ratios were calculated for each variable. Two PRISMA-compliant meta-analyses were also performed: one analyzed studies reporting the cytology results of multiple LPs, and one analyzed the frequency of abnormal CSF findings as predictors of NM. Results All published results describe outcomes in patients with known NM. These results are, therefore, strongly distorted by spectrum bias, which artificially inflates the apparent sensitivity and specificity of those outcomes. Thus, 25 studies report the yield of positive CSF cytology on the first, second, and third LP as 73%, 87%, and 94%, but also do not describe the parameters of the procedure. Our series in patients with suspected NM (the cohort most relevant to the practicing physician) reports 74%, 85%, and 92% for immediately processed, 10 mL or greater, lumbar and ventricular specimens. Similarly, while 50 studies suggested that low CSF glucose, high CSF protein, and suggestive symptoms are associated with NM, we found very poor Sn/Sp for elevated protein (61%/61%), low glucose (35%/85%), elevated lactate (35%/91%), and symptoms consistent with NM (74%/73%). Of these values, only an elevated lactate and symptoms were even marginally helpful in predicting a positive CSF cytology. No variable predicted a negative cytology, and 22.8% of patients with a positive CSF cytology had completely normal CSF findings. Conclusion Generally accepted concepts about the frequency of CSF and clinical findings in patients with suspected NM are based on biased estimates in the literature. No CSF chemistry or clinical finding reliably predicts the presence of NM, and almost a quarter of patients with cytologically proven NM have completely normal findings. In patients with positive CSF cytologies, about 73% are detected after one LP, and more than 90% after 3, but again these findings represent overestimates because of pervasive spectrum bias and differences in sample acquisition/handling. Better diagnostic techniques are desperately needed.
P14.02.A Serum neurofilaments correlate with axonal loss in paclitaxel-induced peripheral neurotoxicity
Authors: R Velasco, C Marco, S Mariotto, A Stradella, J Hernández, A A Argyriou, S Ferrari, J Bruna
Journal: Neuro-Oncology (2022)

Abstract Background Paclitaxel-induced peripheral neuropathy (PIPN) is a dose-limiting axonal polyneuropathy. Nerve conduction studies (NCS) are unique for the assessment of axonal impairment in PIPN. Neurofilaments (NFs), constituent of the neuronal cytoskeleton, are emerging as axonal damage biomarker. To date, the association between changes in NCS and NfL quantification across paclitaxel treatment in breast cancer patients has not been specifically addressed. MATERIAL AND METHODS: Prospective longitudinal measurement of sNfL levels and NCS in 27 chemotherapy-naïve breast cancer patients before (V0) and after completion (V1) of 12 cycles of weekly paclitaxel-based therapy. Results Serum NfL levels (in pg/mL) increased over the course of treatment in the whole of patients (T0: 18,509 +/- 12,886 vs T1:255,805 +/- 194,165, p&amp;lt;0.001). The increase in sNfL levels at T1 showed a significant moderate correlation with the percentage of decrease in the amplitude of the sural (ρ = 0.6205 (p=0.0035), radial (r=0.6134, p=0.005)), ulnar (ρ = 0.6298 (p=0.005)) and peroneal motor (ρ = 0.5676, p=0.024)) nerve in NCS across treatment. Conclusion sNfL levels increase proportionally to the degree of paclitaxel-induced neuroaxonal damage, revealing being a promising blood biomarker able to detect the severity of large nerve fiber degeneration and, therefore, improving the diagnostic accuracy in PIPN.
P17.08.B Single institutional retrospective review of re-irradiation in High Grade Gliomas in a tertiary UK centre
Authors: V Manik, L Brazil, A Swampillai, K Chia, O Al-Salihi
Journal: Neuro-Oncology (2022)

Abstract Background Recurrent high grade gliomas (HGG) pose a treatment challenge as no definite guidelines exist. Re-excision could be appropriate in some cases while systemic therapy options are only a handful. We thus need to resort to the option of re-irradiation at some point but there could be a wide variety of techniques, volumes &amp; doses to choose from due to lack of robust evidence. The UK wide BRIOCHe study for Glioblastoma Multiforme (GBM) will help in providing some standardisation. With this retrospective study, we aim to review our institutional practice with re-irradiation &amp; our patient outcomes. Material and Methods Electronic health records over a period of 3 years from 1 Jun 2019 to 30 May 2021 were searched for patients with HGG that underwent a course of re-irradiation. Various patient factors, tumour &amp; treatment factors at baseline and at recurrence and survival data were collected. Results Total of 8 patients received re-irradiation with all except one having a performance status of 1 at the time of treatment. Seven patients had GBM, one had transformation from baseline G2 glioma and the eighth patient had anaplastic oligodendroglioma (ODG). MGMT was methylated in 62.5% patients while IDH mutation was present only in the transformed glioma. Majority patients had radiotherapy dose of 60Gy/30 fractions with concurrent temozolomide (TMZ) at baseline to a median CTV volume of 186cc. A median of 6 cycles of TMZ were given in the adjuvant setting. Median time to recurrence from completion of adjuvant treatment was 6.7 months (range: 0.9 - 171.6 months). Most recurrences were in the same or an adjacent lobe whereas 1 patient had a multi-focal recurrence. Half the patients at recurrence underwent a re-resection. All patients had salvage chemotherapy at the time of recurrence with a median of 2 regimens and a median of 6 cycles prior to re-irradiation. All patients received a re-irradiation dose of 35Gy in 10 fractions to a median CTV volume of 149cc. The median interval from previous radiotherapy was 18.9 months (range: 11.6 - 190.5 months). The median time to progression from re-RT was 5.4 months (CI: 3.4 - 7.4) and median survival from re-RT was 7 months (CI: 6.2 - 7.8). The median overall survival since diagnosis was 35.1 months (CI: 22.2 - 48.1), one patient was lost to follow up. Conclusion Re-irradiation is a safe &amp; feasible treatment option in carefully selected cases of high grade glioma.
JS04.6.A The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location
Authors: I Liu, L Jiang, E Samuelsson, S Marco Salas, O Hack, D Jeong, M Shaw, B Englinger, J LaBelle, K Ernst, H Palova, P Pokorna, J Sterba, O Slaby, R Geyeregger, D Jones, C Koschmann, J Svedlund, A Resnick, A Diaz, C Haberler, T Czech, I Slavc, J Cotter, K Ligon, S Alexandrescu, W Yung, I Arrillaga-Romany, M Suva, A Beck, J Gojo, M Monje, M Nilsson, M Filbin
Journal: Neuro-Oncology (2022)

Abstract Background Histone 3 lysine27-to-methionine mutations (H3-K27M) frequently occur in childhood diffuse midline gliomas (DMGs) of the pons, thalamus and spinal cord, presumed to be driven by the specific spatiotemporal context of these midline locations during postnatal development. While most common in the pons and at mid-childhood ages, the same oncohistone mutation is recurrently detected in adult DMGs and throughout different midline regions. The potential heterogeneity of tumors at different ages and in different anatomical locations of the midline are vastly understudied. Material and Methods Through dissecting the transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs - spanning the age range from 2-68 years and locations from spinal cord to thalamus - at single cell resolution, we delineate how age- and location-dependent contexts shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. Results We identify that oligodendrocyte precursor (OPC)-like cells constitute the stem-like compartment in H3-K27M DMGs across all clinico-anatomical groups, however, depending on location, display varying levels of maturity resembling less differentiated pre-OPCs or more mature OPCs further differentiated along the oligodendroglial lineage. We further demonstrate increased mesenchymal cell states in adult tumors, which we link to age-related differences in glioma-associated immune cell compartments. We for the first time resolve the spatial organization of H3-K27M DMG cell types in intact patient tissues, identifying a local niche of the oligodendroglial lineage. Conclusion Our study provides a powerful resource for rational modeling and therapeutic frameworks taking into account determinants of age and location in this lethal glioma group.
P01.19.A The temporo-parieto-occipital junction in the non-dominant hemisphere as a challenging hub for glioma surgery: functional and oncological outcomes
Authors: M Conti Nibali, G Puglisi, A Leonetti, M Rossi, L Gay, T Sciortino, L Mattioli, M Gambaretti, L Viganò, L Bello
Journal: Neuro-Oncology (2022)

Abstract Background The temporo-parieto-occipital junction (TPOJ) in the non-dominant hemisphere is a complex region intersected by multiple white matter bundles (Optic radiations, Inferior-fronto-occipital tract, inferior-longitudinalis-tract, superior-longitudinalis-tract, vertical-occipital-tract, medial-dorsal-longitudinal-tract, parietal-aslant-tract), subserving several high-level neurological functions such as spatial recognition, visual agnosia, visual field, attention and working memory. Few data are available on the optimum brain mapping strategy to be adopted for resecting tumors involving this area. Ideally it should allow surgeon to effectively identify several tracts and safely preserve all functions. Material and Methods We developed a proper protocol to approach this complex area integrating, in awake condition, intraoperative visual test (iVT) to mapping visual field, semantic association test (SRAT) to prevent visual agnosia and preserve working memory, hand manipulation task (hMT) to preserve spatial abilities. We reviewed its efficacy in a series of 38 patients with tumors involving non-dominant TPOJ, looking to functional (neurologic-neuropsychological) and oncological (EOR) outcomes. we perform a lesion symptom map and a disconnectome analysis to evaluate what region predict a decline in neuropsychological function and which tract of white brain matter are correlated in the decline of performance. Results Feasibility was high and all patients were able to perform and complete the protocol, which lasted, on the average11 min cortically and 25 min subcortically. Specificity was &amp;gt;95%. Immediate post-operative deficits were documented in 87.4% of patients, permanent in 3.9% (visual field, visual spatial abilities). Attentive and emotional domains were those mostly affected in the neuropsychological evaluation. Lesion symptom mapping and disconnectomic analysis showed that the postoperative decrease in neuropsychological performance was associated with resection of a cluster of voxels corresponding to the anterior portion of the temporo-parietal junction. The white matter tracts mainly involved were the anterior and posterior segment of the middle longitudinal fasciculus (aMdLF and pMdLF) and the parietal aslant tract (PAT). Conclusion Effective and safe resection of tumors involving non-dominant TPOJ is feasible. The adoption of a specific brain mapping protocol in awake setting is recommended to achieve a full functional preservation and extend tumor resection. Further analysis should be performed to assess the role of this subcortical tracts.
P18.02.B Influence of preoperative embolization on intraoperative parameters, hospital stay and neurocognitive outcome compared to surgery alone
Authors: M Pedersen, T Eibl, A Nania, H Voit-Höhne, M Schrey, H Steiner, M Holtmannspötter
Journal: Neuro-Oncology (2022)

Abstract Background Preoperative embolization of meningiomas is used to reduce intraoperative blood loss and facilitate resection. So far, a risk-benefit stratification of this additional intervention on the neurocognitive outcome is missing. This study investigates the influence of preoperative embolization with liquid Embolisate on intraoperative parameters, length of hospital stays and functional outcome. Material and Methods Patients treated for intracranial meningiomas at a single center between January 2019 and June 2021 were reviewed in a retrospective matched-pair analysis. Patients were matched to group A (tumor resected) and group B (preoperatively embolized and tumor resected after 2,27 ± 3,05 days). Matching criteria were tumor diameter and location (convexity, falx cerebri or skull base, frontal, parietal, occipital, temporal). Data collection included MRI (location, tumor- and necrosis volume, edema, complications), DSA (tumor blush, arterial supply), medical history, histological, surgical, clinical course, complications, and haematological parameters, as well as neurocognitive symptoms on admission and discharge from hospital. Results 44 patients with intracranial Meningiomas were included, divides into 2 groups, each encompassing 22 patients (mean age 62,41 years, 40,5% female). The matching criteria tumor diameter (64.21 vs. 63.55 mm, p=0.725) and tumor localisation (p=0.381) showed no significant differences. There were no significant differences in postoperative hospital stay (14.41 ± 9.5 vs. 14.25 ± 16.88 days, p=0.814) and in preoperative perifocal oedema (82% vs. 82%, p=0.397). Preoperative embolization was associated with decreased intraoperative tumor bleeding (67% vs. 14%, p=0.001, PHI= 0.534), longer duration of surgery (4:58 ± 2:44 vs. 06:07 ± 03:00 hours, p=0.037), trend for decrease in perifocal oedema (p=0.052, PHI=0,498), neurocognitive improvement on discharge from hospital (23% vs. 86%, p=0.045, PHI=0.339) and decreased of epileptic seizures (preoperative 18% vs. 18% and postoperative 23% vs. 5%). There was no increase in cumulative complication rate (p=1.0) and no long-term neurocognitive impairments associated with embolization. Conclusion This study suggests that preoperative embolization of intracranial meningiomas significantly decreased intraoperative tumor blood loss but is also associated to an improvement on neurocognitive abilities compared to surgery alone. Importantly, complication rate is not increased. In the future, larger studies and perhaps a randomised control trial might be of value in corroborating these findings. Furthermore, the neurocognitive symptoms should be assessed in a standardised examination form, qualitative parameters such as bleeding tendency should be supplemented by quantifiable parameters, e.g., blood loss in ml.